Evidence-based guidelines needed for perioperative antithrombotic management in TJA

Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are increasingly common orthopaedic procedures, with projected annual growth rates of 5.2% and 4.4%, respectively. As with all major surgeries, there is an inherent balance of thrombotic and hemorrhagic risks postoperatively.

Although there is an expansive pharmaceutical cascade of drugs emerging on the market for potent blood thinning, patients taking antithrombotic medications present a unique challenge in total joint arthroplasty (TJA), as their baseline risk for both hemorrhagic and thromboembolic events is elevated.

However, most guidelines relating to the balance between hemorrhagic and thrombotic risks in TJA are from non-arthroplasty societies, including cardiology, anesthesiology, and pulmonology.

Consequently, arthroplasty surgeons are tasked with decisions on preoperative interruptions and resumptions of antithrombotic regimens. This introduces significant variability in clinical practice, complicates patient care, and precludes standardized arthroplasty pathways with evidence-based strategies to help maximize patient outcomes.

Antiplatelet and anticoagulation medications
Antiplatelet agents inhibit platelet adhesion, activation, and aggregation, disrupting thrombus formation. Common targets of antiplatelets include thromboxane A2 (aspirin) and the P2Y12 receptor (clopidogrel, prasugrel, ticagrelor). Aspirin irreversibly inhibits cyclooxygenase, blocking thromboxane A2 production and inactivating platelets for seven to 10 days, with hemostasis recovering within two to three days of discontinuation. P2Y12 inhibitors block adenosine diphosphate binding, with clopidogrel and prasugrel acting irreversibly (seven- to 10-day hemostasis recovery) and ticagrelor acting reversibly (three- to five-day hemostasis recovery). Less common agents include cilostazol and dipyridamole, which inhibit aggregation via increased cAMP and cause vasodilation.

Anticoagulants prevent thrombin formation and fibrin clot stabilization. Warfarin, a vitamin K antagonist, has largely been replaced by direct oral anticoagulants (DOACs), such as dabigatran, apixaban, and rivaroxaban, which directly inhibit thrombin or factor Xa. DOACs have rapid onset and shorter half-lives, allowing hemostasis recovery within two to three days, versus three to four days with warfarin. Diet does not impact DOACs’ efficacy, and they have fewer drug interactions. Heparins (unfractionated and low-molecular-weight heparin [LMWH]) activate antithrombin. Hemostasis recovers within four and 12 to 24 hours after unfractionated heparin and LMWH discontinuation, respectively. These agents are often used acutely and for warfarin bridging, rather than for chronic anticoagulation.

Current guidelines and the need for more data
At the 2022 International Consensus Meeting on Venous Thromboembolism (VTE), the hip and knee delegates formally recommended low-dose oral aspirin (81 mg bid) over the prior mainstay of LMWH (enoxaparin, subcutaneous) for routine postoperative chemical thromboprophylaxis. Aspirin demonstrated clear contemporary evidence in reducing the risk of VTE without increasing rates of postoperative bleeding-related complications. However, this recommendation does not extend to patients on preoperative antithrombotic medications, and the ideal management of these medications remains unclear.

Preoperative antithrombotic management guidelines are largely informed by the American Society of Regional Anesthesia and Pain Medicine (ASRA) and the risk associated with neuraxial anesthesia (Table 1). In 2018, ASRA advised continuing aspirin through the perioperative period and discontinuing P2Y12 inhibitors five to seven days before surgery if neuraxial anesthesia is planned.

Concerning DOACs, ASRA recommended discontinuation two days prior to surgery due to spinal hematoma risk with neuraxial anesthesia, with dabigatran contraindicating neuraxial anesthesia entirely.

The 2018 ASRA guidelines do not discuss the postoperative resumption of antithrombotic regimens, leaving current management primarily guided by non-orthopaedic societies and surgeon experience. The American College of Chest Physicians and American College of Surgeons recommend resuming DOACs at least 24 hours after surgery and resuming P2Y12 inhibitors within 24 hours, with stipulations by ASRA to wait at least six hours after neuraxial anesthesia.

Notably, these recommendations are supported and based on the PAUSE cohort trial, which resumed DOACs 48 to 72 hours post-surgery without heparin bridging. However, orthopaedic procedures represented only 11.4% of all procedures in the PAUSE trial, with TJA comprising only a subset of those procedures. Furthermore, this study was specific to patients with atrial fibrillation, who may exhibit different risk profiles compared to patients on chronic anticoagulation for other indications.

Finally, the PAUSE trial did not investigate the effects of half versus full dosage on anticoagulation resumption. Thus, although the PAUSE trial represents the best current evidence for chronic anticoagulation management in the perioperative period, it has significant limitations that weaken its applicability for TJA.

On the other hand, the PEPPER trial is an ongoing clinical trial investigating VTE prevention and all-cause mortality after TJA with aspirin, warfarin, and rivaroxaban prophylaxis. This large trial of 20,000 patients is expected to be completed this year. The published results may provide further guidance on this challenging question, although it is currently unclear how many patients included will be on preoperative antithrombotic agents.

Despite the growing body of literature on perioperative antithrombotic management and postoperative aspirin usage in antithrombotic-naive patients, there remains a striking absence of formal guidance regarding the optimal timing to resume chronic antithrombotic agents. To date, this decision remains a “best guess” approach, relying on individual surgeon judgment in the absence of strong evidence-based protocols.

The arthroplasty community, therefore, needs prospective studies and formal guidelines that balance medical complications with TJA complications relating to persistent hemarthrosis, seromas, and delayed wound healing.

Theodor Di Pauli von Treuheim, MD, is an orthopaedic surgery resident at NYU Langone Orthopedics. He is in the process of applying for a fellowship to enhance his subspecialty training in adult reconstruction and is focused on optimizing perioperative care pathways for arthroplasty patients.

Benjamin Padon, BS, is a fourth-year medical student at NYU Grossman School of Medicine. He is currently applying for residency in arthopaedic surgery and is excited for a potential career in the field.

Anzar Sarfraz, MD, is a clinical research fellow with the adult reconstruction team at NYU Langone Orthopedics. He is focused on improving patient-reported outcomes and reducing infection rates after total joint arthroplasty, with several ongoing projects in these areas.

Garrett Ruff, BS, is a fourth-year medical student at NYU Grossman School of Medicine. He is currently applying for residency in orthopaedic surgery and is excited for a potential career in the field.

Vinay K. Aggarwal, MD, is an associate professor of orthopaedic surgery and the adult reconstruction fellowship director at NYU Langone Orthopedics. He is the chief of the Adult Reconstruction Service at Bellevue Hospital and is interested in arthroplasty outcomes research with a special focus on complication prevention.

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